Calculating pH-dependent free energy of proteins by using Monte Carlo protonation probabilities of ionizable residues
Protein & Cell
; (12): 230-238, 2012.
Article
en En
| WPRIM
| ID: wpr-757283
Biblioteca responsable:
WPRO
ABSTRACT
Protein folding, stability, and function are usually influenced by pH. And free energy plays a fundamental role in analysis of such pH-dependent properties. Electrostatics-based theoretical framework using dielectric solvent continuum model and solving Poisson-Boltzmann equation numerically has been shown to be very successful in understanding the pH-dependent properties. However, in this approach the exact computation of pH-dependent free energy becomes impractical for proteins possessing more than several tens of ionizable sites (e.g. > 30), because exact evaluation of the partition function requires a summation over a vast number of possible protonation microstates. Here we present a method which computes the free energy using the average energy and the protonation probabilities of ionizable sites obtained by the well-established Monte Carlo sampling procedure. The key feature is to calculate the entropy by using the protonation probabilities. We used this method to examine a well-studied protein (lysozyme) and produced results which agree very well with the exact calculations. Applications to the optimum pH of maximal stability of proteins and protein-DNA interactions have also resulted in good agreement with experimental data. These examples recommend our method for application to the elucidation of the pH-dependent properties of proteins.
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Unión Proteica
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Protones
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Termodinámica
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ADN
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Catepsina B
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Proteínas
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Muramidasa
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Química
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Método de Montecarlo
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Probabilidad
Tipo de estudio:
Health_economic_evaluation
Idioma:
En
Revista:
Protein & Cell
Año:
2012
Tipo del documento:
Article